AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity.
Identifieur interne : 000B11 ( Main/Exploration ); précédent : 000B10; suivant : 000B12AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity.
Auteurs : Dan Liang [États-Unis] ; Lin Tian [États-Unis] ; Ran You [États-Unis] ; Matthew M. Halpert [États-Unis] ; Vanaja Konduri [États-Unis] ; Yunyu C. Baig [États-Unis] ; Silke Paust [États-Unis] ; Doyeun Kim [Corée du Sud] ; Sunghoon Kim [Corée du Sud] ; Fuli Jia [États-Unis] ; Shixia Huang [États-Unis] ; Xiang Zhang [États-Unis] ; Farrah Kheradmand [États-Unis] ; David B. Corry [États-Unis] ; Brian E. Gilbert [États-Unis] ; Jonathan M. Levitt [États-Unis] ; William K. Decker [États-Unis]Source :
- Frontiers in immunology [ 1664-3224 ] ; 2017.
Abstract
Dendritic cells (DCs) must integrate a broad array of environmental cues to exact control over downstream immune responses including TH polarization. The multienzyme aminoacyl-tRNA synthetase complex component AIMp1/p43 responds to cellular stress and exerts pro-inflammatory functions; however, a role for DC-expressed AIMp1 in TH polarization has not previously been shown. Here, we demonstrate that the absence of AIMp1 in bone marrow-derived DC (BMDC) significantly impairs cytokine and costimulatory molecule expression, p38 MAPK signaling, and TH1 polarization of cocultured T-cells while significantly dysregulating immune-related gene expression. These deficits resulted in significantly compromised BMDC vaccine-mediated protection against melanoma. AIMp1 within the host was also critical for innate and adaptive antiviral immunity against influenza virus infection in vivo. Cancer patients with AIMp1 expression levels in the highest tertiles exhibited a 70% survival advantage at 15-year postdiagnosis as determined by bioinformatics analysis of nearly 9,000 primary human tumor samples in The Cancer Genome Atlas database. These data establish the importance of AIMp1 for the effective governance of antitumor and antiviral immune responses.
DOI: 10.3389/fimmu.2017.01801
PubMed: 29379495
Affiliations:
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<front><div type="abstract" xml:lang="en">Dendritic cells (DCs) must integrate a broad array of environmental cues to exact control over downstream immune responses including T<sub>H</sub>
polarization. The multienzyme aminoacyl-tRNA synthetase complex component AIMp1/p43 responds to cellular stress and exerts pro-inflammatory functions; however, a role for DC-expressed AIMp1 in T<sub>H</sub>
polarization has not previously been shown. Here, we demonstrate that the absence of AIMp1 in bone marrow-derived DC (BMDC) significantly impairs cytokine and costimulatory molecule expression, p38 MAPK signaling, and T<sub>H</sub>
1 polarization of cocultured T-cells while significantly dysregulating immune-related gene expression. These deficits resulted in significantly compromised BMDC vaccine-mediated protection against melanoma. AIMp1 within the host was also critical for innate and adaptive antiviral immunity against influenza virus infection <i>in vivo</i>
. Cancer patients with AIMp1 expression levels in the highest tertiles exhibited a 70% survival advantage at 15-year postdiagnosis as determined by bioinformatics analysis of nearly 9,000 primary human tumor samples in The Cancer Genome Atlas database. These data establish the importance of AIMp1 for the effective governance of antitumor and antiviral immune responses.</div>
</front>
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<li>États-Unis</li>
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<region><li>Région capitale de Séoul</li>
<li>Texas</li>
</region>
<settlement><li>Séoul</li>
</settlement>
<orgName><li>Université nationale de Séoul</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Texas"><name sortKey="Liang, Dan" sort="Liang, Dan" uniqKey="Liang D" first="Dan" last="Liang">Dan Liang</name>
</region>
<name sortKey="Baig, Yunyu C" sort="Baig, Yunyu C" uniqKey="Baig Y" first="Yunyu C" last="Baig">Yunyu C. Baig</name>
<name sortKey="Corry, David B" sort="Corry, David B" uniqKey="Corry D" first="David B" last="Corry">David B. Corry</name>
<name sortKey="Decker, William K" sort="Decker, William K" uniqKey="Decker W" first="William K" last="Decker">William K. Decker</name>
<name sortKey="Gilbert, Brian E" sort="Gilbert, Brian E" uniqKey="Gilbert B" first="Brian E" last="Gilbert">Brian E. Gilbert</name>
<name sortKey="Halpert, Matthew M" sort="Halpert, Matthew M" uniqKey="Halpert M" first="Matthew M" last="Halpert">Matthew M. Halpert</name>
<name sortKey="Huang, Shixia" sort="Huang, Shixia" uniqKey="Huang S" first="Shixia" last="Huang">Shixia Huang</name>
<name sortKey="Jia, Fuli" sort="Jia, Fuli" uniqKey="Jia F" first="Fuli" last="Jia">Fuli Jia</name>
<name sortKey="Kheradmand, Farrah" sort="Kheradmand, Farrah" uniqKey="Kheradmand F" first="Farrah" last="Kheradmand">Farrah Kheradmand</name>
<name sortKey="Konduri, Vanaja" sort="Konduri, Vanaja" uniqKey="Konduri V" first="Vanaja" last="Konduri">Vanaja Konduri</name>
<name sortKey="Levitt, Jonathan M" sort="Levitt, Jonathan M" uniqKey="Levitt J" first="Jonathan M" last="Levitt">Jonathan M. Levitt</name>
<name sortKey="Paust, Silke" sort="Paust, Silke" uniqKey="Paust S" first="Silke" last="Paust">Silke Paust</name>
<name sortKey="Tian, Lin" sort="Tian, Lin" uniqKey="Tian L" first="Lin" last="Tian">Lin Tian</name>
<name sortKey="You, Ran" sort="You, Ran" uniqKey="You R" first="Ran" last="You">Ran You</name>
<name sortKey="Zhang, Xiang" sort="Zhang, Xiang" uniqKey="Zhang X" first="Xiang" last="Zhang">Xiang Zhang</name>
</country>
<country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Kim, Doyeun" sort="Kim, Doyeun" uniqKey="Kim D" first="Doyeun" last="Kim">Doyeun Kim</name>
</region>
<name sortKey="Kim, Sunghoon" sort="Kim, Sunghoon" uniqKey="Kim S" first="Sunghoon" last="Kim">Sunghoon Kim</name>
</country>
</tree>
</affiliations>
</record>
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